Discharge chambers and ionization devices, methods and systems using them

ABSTRACT

Certain configurations of plasma discharge chambers and plasma ionization sources comprising a plasma discharge chamber are described. In some examples, the discharge chamber comprises a conductive area and is configured to sustain a plasma discharge within the discharge chamber. In other examples, the discharge chamber comprises at least one inlet configured to receive a plasma gas and at least one outlet configured to provide ionized analyte from the discharge chamber. Systems and methods using the discharge chambers are also described.

PRIORITY APPLICATION

The application is related to, and claims priority to and the benefitof, U.S. Provisional Application No. 62/673,513 filed on May 18, 2018,the entire disclosure of which is hereby incorporated herein byreference.

TECHNOLOGICAL FIELD

The technology described herein is related to ionization devices,methods and systems. More particularly, some configurations of plasmadischarge ionization sources and systems and methods using them arediscussed.

BACKGROUND

Ionization techniques are often used in the analysis of variousanalytes. Ionization of the analyte can often lead to extensivefragmentation.

SUMMARY

Certain aspects, embodiments, configurations and features of ionizationdevices, methods and systems are described herein.

In one aspect, a plasma discharge ionization source is provided. Incertain configurations, the ionization source comprises a dischargechamber configured to electrically couple to a power source andconfigured to sustain a plasma discharge within the discharge chamber,wherein the discharge chamber comprises at least one inlet configured toreceive a plasma gas, and at least one outlet configured to provideionized analyte from the discharge chamber.

In certain examples, the plasma discharge ionization source furthercomprises at least one bend between the at least one inlet and the atleast one outlet, and wherein the at least one bend is configured toreduce a number of metastable atoms and free electrons and photonsexiting the discharge chamber through the at least one outlet. In someembodiments, the at least one bend is configured as bend of aboutninety-degrees. In other embodiments, the plasma discharge ionizationsource further comprises a second bend positioned upstream of the atleast one bend or positioned downstream of the at least one bend.

In some instances, the plasma discharge ionization source furthercomprises a first electrode electrically coupled to the dischargechamber, wherein the first electrode is configured to electricallycouple to the power source. In other examples, the first electrode ispositioned within the at least one inlet of the discharge chamber. Insome embodiments, the plasma discharge ionization source furthercomprises a second electrode electrically coupled to the dischargechamber.

In some examples, the discharge chamber comprises one or more conductivematerials, e.g., a stainless steel, tungsten, a nickel chromium alloy,nickel chromium molybdenum alloy, titanium, a titanium alloy andcombinations thereof.

In certain embodiments, the inlet is configured to simultaneouslyreceive the plasma gas and a sample comprising an analyte. In otherembodiments, the plasma discharge ionization source further comprises asecond inlet separate from the inlet, wherein the second inlet isconfigured to provide a sample comprising an analyte into the dischargechamber. In some examples, the discharge chamber comprises a firstsection adjacent to the at least one inlet, a third section adjacent tothe at least one outlet and a second section between the first sectionand the third section.

In other examples, an average inner diameter of the third section islarger than an average inner diameter of the second section. In someembodiments, an average inner diameter of the second section is largerthan an average inner diameter of the first section.

In other embodiments, the discharge chamber further comprises a secondinlet configured to receive a second plasma gas. In certain examples,the discharge chamber is configured to sustain the plasma dischargewithout any inductive coupling.

In some configurations, the plasma discharge ionization source furthercomprises a second discharge chamber fluidically coupled to thedischarge chamber, wherein the second discharge chamber comprises atleast one bend between an inlet section and an outlet section of thesecond discharge chamber. In certain examples, the at least one bend ofthe second discharge chamber comprises a different geometry than the atleast one bend of the discharge chamber.

In certain examples, the plasma discharge ionization source furthercomprises an electrode electrically coupled to the second dischargechamber. In some embodiments, the second discharge chamber is configuredto sustain a plasma discharge with a second plasma gas different thanthe plasma gas. In certain examples, the discharge chamber can beconfigured to receive two or more different plasma gases to selectivelyionize different analyte species using the different plasma gases.

In another aspect, a mass spectrometer system comprises a plasmadischarge ionization source. The plasma discharge ionization source maycomprise a discharge chamber configured to electrically couple to apower source, wherein the discharge chamber is configured to sustain aplasma discharge within the discharge chamber, and wherein the dischargechamber comprises at least one inlet configured to receive a plasma gas,and at least one outlet configured to provide ionized analyte from thedischarge chamber. The mass spectrometer system may also comprise a massanalyzer fluidically coupled to the at least one outlet of the dischargechamber and configured to receive ionized analyte from the dischargechamber.

In certain examples, the discharge chamber further comprises a firstelectrode electrically coupled to the discharge chamber, wherein thefirst electrode is configured to electrically couple to the powersource. In some examples, the discharge chamber is directly coupled toan inlet orifice of the mass analyzer.

In other examples, the mass analyzer comprises at least one quadrupoleassembly fluidically coupled to the outlet of the discharge chamber. Insome instances, the mass analyzer comprises a triple quadrupoleassembly. In other instances, the mass spectrometer system comprises atleast one pumping stage between the outlet of the discharge chamber andan inlet of the triple quadrupole assembly. In some examples, a firstquadrupole assembly of the triple quadrupole assembly is fluidicallycoupled to the at least one pumping stage, and wherein the firstquadrupole assembly is configured as a mass filter. In other instances,a second quadrupole assembly of the triple quadrupole assembly isfluidically coupled to the first quadrupole assembly, and wherein thesecond quadrupole assembly is configured as a collision quadrupoleassembly. In some embodiments, a third quadrupole assembly of the triplequadrupole assembly is fluidically coupled to the second quadrupoleassembly, and wherein the third quadrupole assembly is configured as amass filter.

In some examples, the mass spectrometer system further comprises adetector fluidically coupled to the third quadrupole assembly. Incertain embodiments, the mass spectrometer system further comprises aprocessor electrically coupled to the discharge chamber, wherein theprocessor is configured to provide a first voltage to the dischargechamber to sustain the plasma discharge within the discharge chamber. Insome examples, the processor is configured to provide a second voltage,different than the first voltage, to sustain the plasma discharge withinthe discharge chamber. In some configurations, the processor is furtherconfigured to provide the plasma gas to the discharge chamber. Incertain embodiments, the processor is further configured to provide asecond plasma gas, different than the plasma gas, to the dischargechamber.

In certain embodiments, the discharge chamber of the mass spectrometermay comprise a first section adjacent to the at least one inlet, a thirdsection adjacent to the at least one outlet and a second section betweenthe first section and the third section. In other embodiments, anaverage inner diameter of the third section is larger than an averageinner diameter of the second section, and wherein an average innerdiameter of the second section is larger than an average inner diameterof the first section.

In some examples, the discharge chamber of the mass spectrometer furthercomprises at least one bend between the at least one inlet and the atleast one outlet, and wherein the at least one bend is configured toreduce a number of metastable atoms and free electrons exiting thedischarge chamber through the at least one outlet.

In certain examples, the mass spectrometer system further comprises asecond discharge chamber fluidically coupled to the discharge chamber,wherein the second discharge chamber comprises at least one bend betweenan inlet section and an outlet section of the second discharge chamber.

In some embodiments, the mass spectrometer system further comprises achromatography system fluidically coupled to the at least one inlet ofthe discharge chamber. In certain examples, the chromatography system isconfigured as a gas chromatography system or a liquid chromatographysystem.

In another aspect, a method comprises ionizing an analyte by introducingthe analyte into a plasma discharge sustained within a discharge chambercomprising a first electrode, wherein the discharge chamber comprises atleast one inlet and at least one outlet, and wherein the plasmadischarge is sustained within the discharge chamber by providing avoltage to the first electrode in the presence of a plasma gasintroduced into the discharge chamber through the at least one inlet ofthe discharge chamber.

In certain embodiments, the method comprises configuring the firstelectrode to be positioned within the at least one inlet of thedischarge chamber. In some examples, the method comprises providing adirect current voltage of about +/−10 Volts to about +/−5000 Volts tothe first electrode. In other examples, the method comprises providingan alternating current voltage of about +/−20 Volts to about +/−3000Volts to the first electrode. In some instances, the method comprisesproviding a radio frequency current to the first electrode, wherein afrequency of the radio frequency is about 100 Hz to about 10 MHz. Thevoltages and frequencies provided herein are merely illustrative, andother voltages and frequencies will be selected by the person ofordinary skill in the art, given the benefit of this disclosure.

In other examples, the method comprises sustaining the plasma dischargewithin the discharge chamber at a suitable pressure to sustain theplasma discharge, e.g., one example may use a pressure of about 10⁻³-100Torr. In some embodiments, the method comprises providing the plasmadischarge using a plasma gas flow rate of 500 sccm or less, though flowrates other than this exemplary flow rate may also be used.

In some examples, the method comprises configuring the discharge chamberwith a first section adjacent to the at least one inlet, a third sectionadjacent to the at least one outlet and a second section between thefirst section and the third section, wherein an average inner diameterof the third section is larger than an average inner diameter of thesecond section.

In certain examples, the method comprises selecting the provided voltageto promote production of a parent analyte ion of the ionized analyte topermit quantitation of the analyte using a parent analyte ionmass-to-charge peak intensity.

In some embodiments, the method comprises monitoring a current providedto the first electrode to determine if the plasma discharge is sustainedwithin the discharge chamber. In certain examples, the method comprisesusing an optical sensor to determine if the plasma discharge issustained within the discharge chamber.

In some configurations, the plasma gas can be one or more of helium,neon, argon, krypton, xenon, nitrogen, nitric oxide, ammonia, oxygen,air, compressed air, hydrogen, methane, carbon monoxide, carbon dioxide,nitrous oxide, and nitrogen dioxide. These illustrative plasma gases areprovided as exemplary and not intended to exclude other plasma gasesthat might also be used, e.g., rare earth gases, rare earth gasmixtures, etc.

In certain examples, the method comprises introducing the analyte intothe discharge chamber to ionize the introduced analyte using a firstplasma gas, permitting the ionized analyte to exit the discharge chamberthrough the at least one outlet prior to introduction of a secondanalyte into the discharge chamber, and introducing the second analyteinto the discharge chamber to ionize the introduced second analyte usinga second plasma gas different from the first plasma gas. In someinstances, the method comprises permitting the ionized second analyte toexit the discharge chamber through the at least one outlet prior tointroduction of a third analyte into the discharge chamber, andintroducing the third analyte into the discharge chamber to ionize theintroduced third analyte using a third plasma gas different from thefirst plasma gas and the second plasma gas. Each of the first and secondplasma gas can independently be one or more of helium, neon, argon,krypton, xenon, nitrogen, nitric oxide, ammonia, oxygen, air, compressedair, hydrogen, methane, carbon monoxide, carbon dioxide, nitrous oxide,and nitrogen dioxide.

In certain examples, the method comprises introducing the analyte intothe discharge chamber to ionize the introduced analyte using a firstvoltage provided to the at least one electrode, permitting the ionizedanalyte to exit the discharge chamber through the at least one outletprior to introduction of a second analyte into the discharge chamber,and introducing the second analyte into the discharge chamber to ionizethe introduced second analyte using a second voltage different from thefirst voltage. In some embodiments, the method comprises permitting theionized second analyte to exit the discharge chamber through the atleast one outlet prior to introduction of a third analyte into thedischarge chamber, and introducing the third analyte into the dischargechamber to ionize the introduced third analyte using a third voltagedifferent from the first voltage and the second voltage. In someexamples, the method comprises altering a composition of the plasma gasprior to introduction of the second analyte into the discharge chamber.

In other embodiments, the method comprises configuring the dischargechamber to comprise and at least one bend between the at least one inletand the at least one outlet

In some examples, the method comprises coupling the discharge chamber toa second discharge chamber, wherein the second discharge chamber iselectrically coupled to a second electrode, wherein the second dischargechamber comprises at least one inlet, and at least one outlet, andwherein a plasma discharge is sustained within the second dischargechamber by providing a voltage to the second electrode in the presenceof a plasma gas. In some configurations, the second discharge chambercan be configured with at least one bend between the at least one inletof the second discharge chamber and the at least one outlet of thesecond discharge chamber. The methods described herein can be used tosustain the plasma discharge in the discharge chamber without anyinductive coupling.

In an additional aspect, a kit is provided that comprises one or more ofthe plasma discharge ionization sources described herein andinstructions for using the plasma discharge ionization source provide aplasma discharge within the discharge chamber.

In another aspect, a method of facilitating ionization of an analyte isdescribed. In some examples, the method comprises providing a dischargechamber configured to sustain a plasma discharge within the dischargechamber, the discharge chamber configured to electrically couple to atleast one electrode configured to couple to a power source, thedischarge chamber further comprising at least one inlet and at least oneoutlet, and wherein the discharge chamber is configured to sustain theplasma discharge within the discharge chamber using a voltage providedto the at least one electrode.

In an additional aspect, a method of facilitating ionization of ananalyte comprises providing a discharge chamber configured to sustain aplasma discharge within the discharge chamber, wherein the dischargechamber is configured to electrically couple to at least one electrodeconfigured to couple to a power source. The discharge chamber mayfurther comprise at least one inlet, at least one outlet and optionallyat least one bend between the at least one inlet and the at least oneoutlet. The discharge chamber can be configured to sustain the plasmadischarge within the discharge chamber using a voltage provided to theat least one electrode.

In another aspect, a method of quantitating an analyte in a samplecomprises measuring a peak intensity of a parent analyte ion producedfrom ionization of the analyte after introducing the analyte into aplasma discharge produced within a discharge chamber by using a plasmagas flow rate of 500 sccm or less. In some examples, the plasma gas canbe selected to enhance production of the parent analyte ion using theproduced plasma discharge.

In an additional aspect, a method of ionizing of an analyte to enhanceproduction of a parent analyte ion comprises introducing the analyteinto a plasma discharge sustained in a discharge chamber using a plasmagas provided to the discharge chamber and a voltage provided to thedischarge chamber. In some configurations, the plasma discharge can besustained within the discharge chamber using a plasma gas flow of 500sccm or less. In some instances, the plasma discharge comprises anaverage temperature of about 2000 Kelvin or less.

In another aspect, a plasma discharge comprising an average temperatureof about 2000 Kelvin or less is described. In some embodiments, theplasma discharge can be sustained within a discharge chamber using avoltage provided to the discharge chamber in the presence of a providedplasma gas at a plasma gas flow rate of 500 sccm or less.

In another aspect, a plasma discharge is provided that is configured toprovide both positive and negative analyte ions without altering avoltage provided to sustain the plasma discharge.

Additional aspects, configurations, embodiments and examples aredescribed in more detail below.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

Certain specific configurations of devices, systems and methods aredescribed below with reference to the accompanying figures in which:

FIG. 1 is one illustration of a discharge chamber or tube configured tosustain a discharge ionization source, in accordance with certainexamples;

FIG. 2A is an illustration showing an electrode positioned within aninlet of a discharge chamber, in accordance with certain embodiments;

FIG. 2B is an illustration showing an electrode positioned within aninlet of a discharge chamber and a second electrode present in thedischarge chamber, in accordance with certain embodiments;

FIG. 3A is an illustration showing a discharge chamber comprising a hardbend, in accordance with some embodiments;

FIG. 3B is an illustration showing a discharge chamber comprising a softbend, in accordance with some embodiments;

FIG. 4A is an illustration of a discharge chamber comprising two bends,in accordance with certain examples;

FIG. 4B is an illustration of a discharge chamber comprising threebends, in accordance with some examples;

FIG. 4C is an illustration of a discharge chamber comprising two bendsof different configurations, in accordance with some examples;

FIG. 5A is an illustration of a discharge chamber comprising two inlets,in accordance with some configurations;

FIG. 5B is another illustration of a discharge chamber comprising twoinlets, in accordance with certain examples;

FIG. 5C is an illustration of a discharge chamber comprising twooutlets, in accordance with some examples;

FIG. 6A is an illustration of a straight chamber comprising a variablediameter, in accordance with some examples;

FIG. 6B is another illustration of a straight chamber comprising avariable diameter, in accordance with some configurations;

FIG. 6C is an illustration of a straight chamber with a variablediameter, in accordance with some examples;

FIG. 6D is an illustration of a bent chamber with a variable diameter,in accordance with certain instances;

FIG. 7A is an illustration of two discharge chambers coupled to eachother, in accordance with some examples;

FIG. 7B is another illustration of two discharge chambers coupled toeach other, in accordance with some examples;

FIG. 7C is an illustration of two discharge chambers in parallel, inaccordance with some examples;

FIG. 8 is an illustration of a discharge chamber comprising an opticalwindow, in accordance with some examples;

FIG. 9A is an illustration of a gas chromatography system fluidicallycoupled to a discharge chamber, in accordance with some examples;

FIG. 9B is an illustration of a liquid chromatography system fluidicallycoupled to a discharge chamber, in accordance with some examples;

FIG. 10 is an illustration of a mass spectrometry system comprising adischarge chamber, in accordance with certain examples;

FIG. 11 is an illustration of a discharge chamber, in accordance withsome examples;

FIG. 12 is another illustration of a discharge chamber, in accordancewith some examples;

FIG. 13 is an illustration of a discharge chamber fluidically coupled toa triple quadrupole assembly, in accordance with some embodiments;

FIG. 14 is mass spectrum that can be obtained using electron ionizationand showing little precursor ion, in accordance with some examples;

FIGS. 15A, 15B, and 15C show mass spectra of different molecules, inaccordance with certain embodiments; and

FIGS. 16A and 16B show mass spectra obtained using the dischargechambers described herein, and FIG. 16C shows the same spectrum as FIG.14 for comparison purposes.

It will be recognized by the person of ordinary skill in the art, giventhe benefit of this disclosure, that the lengths, widths and otherdimensions of the discharge chambers are not necessarily to scale. Thelength or width of any one region may vary or be different than thelength or width of any other region. Further, the three-dimensionalshape of any one region may be different than other regions and may notnecessarily be depicted in the two-dimensional figures shown.

DETAILED DESCRIPTION

Certain methods, devices and systems are described herein which aredirected to ionization devices and systems that may more gently ionizeone or more analytes. For example, conventional electron ionization (EI)sources can use very high energy to cause molecules to undergo extensivefragmentation. Extensive fragmentation of a molecule into daughter ionscan result in overlap of different analyte fragments rendering itdifficult to determine the identity and/or amount of the originalmolecule in a sample. By selecting the ionization device and theionization conditions using the methods and devices described herein,softer ionization can be implemented to produce more precursor or parentions, e.g., intact molecular ions without extensive fragmentation. Thepresence of enhanced levels of the precursor ions can provide certainattributes including, but not limited to, more accurate identificationof the molecules in unknown samples and increased precision inquantifying an amount of each molecule present in an unknown sample.

Various discharge “tubes” or chambers are described to illustrate someof the many different configurations that can be used to provide softerionization of molecules. The exact dimensions, materials and shapes ofthe tubes may vary. In some examples, the tube may be a “straight” tube,e.g., generally coaxial without any substantial bends, whereas in otherinstances the tube may be bent, e.g., comprise one or more bends. Theinternal diameter of the chamber or tube may increase or decrease froman inlet end to an outlet end as desired. Further, an increase indiameter in one portion of the chamber or tube could be followed by adecrease in diameter in another portion of the tube. The chambers ortubes may be optically transparent, optically opaque or comprise one ormore optical windows to permit visualization of a plasma dischargewithin the tube. Both positive and negative ions can be produced usingthe chambers or tubes without needing to alter the voltages provided tosustain the plasma discharge. The chamber or tube may comprise one, twoor more inlets and one, two or more outlets. As noted in more detailbelow, one or more portions of the chamber or tube may be conductive,but the entire chamber or tube need not be conductive and differentconductive portions of the chamber or tube can be separated bynon-conductive areas as desired. The discharge chamber can be configuredto sustain a plasma discharge using a voltage and a plasma gas, e.g., byproviding a voltage to some portion of the discharge chamber or anelectrode used with the discharge chamber. The plasma discharge can besustained, for example, without any inductive coupling.

In certain examples and referring to FIG. 1, a straight chamber or tube100 is shown comprising a body 105, an inlet 110 and an outlet 115. Thechamber 100 comprises a conductive area 112 adjacent to the inlet 110and a conductive area 117 adjacent to the outlet 115. A voltage can beprovided to the conductive area 112 and the conductive area 117 may beelectrically coupled to ground. As a plasma gas is introduced into thechamber 100 through the inlet 110, a plasma discharge 125 can besustained within the chamber 100. Depending on the plasma gas used, thedischarge 125 can produce metastable atoms and ions. As an analyte isintroduced into the chamber 100, the analyte molecules can collide withthe electrons, metastable atoms and ions and form analyte ions, forexample, by electron impact, penning ionization and/or charge transfer.The flow of plasma gas from the inlet 110 to the outlet 115 cantransport the analyte ions down the chamber 100 and avoid their loss asa result of collision with the sides of the chamber 100. Metastableatoms and free electrons may impact the walls, be redirected or beremoved using other means so they do not enter into a downstreamcomponent of the system to any substantial degree. A difference betweenthe ionization potential of the plasma gas and the analyte generallydefines the sensitivity of ionization as well as degree offragmentation. By selecting the particular plasma gas used, selectiveionization can be achieved for different analytes.

In some embodiments and referring to FIG. 2A, the discharge chamber ortube may be rendered conductive by electrically coupling an electrode tothe inlet end of the chamber. The discharge chamber 200 comprises someportion of area which is conductive. An electrode 210 is shown as beingcoupled to an inlet 202 of the discharge chamber 200 by way of a probe,which can act to electrically isolate the electrode 210 from thedischarge chamber 200. The discharge chamber 200 can be electricallycoupled to chassis ground or ground 225. When a voltage is provided tothe electrode 210 in the presence of a plasma gas, a plasma discharge230 can be sustained within some portion of the chamber 200. Dependingon the voltage provided and/or the provided plasma gas, the ionizationpotential of the plasma discharge 230 may be tuned or varied. Thistuning provides a more controlled way to ionize molecules introducedinto the chamber 200, and different analyte molecules may be introducedinto a plasma discharge sustained with different plasma gases to alterthe overall type and nature of ions produced from the analyte molecules.The exact dimensions of the electrode may vary depending on thedimensions of the inlet. For example, an electrode with a diameter ofabout 1-3 mm may be used, though the size may be smaller or largerdepending on the dimensions of the discharge chamber.

In certain examples and referring to FIG. 2B, a discharge tube orchamber may comprise two or more separate electrodes. The dischargechamber 250 comprises a first electrode 260 and a second electrode 265spatially separated from the first electrode 260. The second electrode265 can be electrically coupled to ground or may be provided with avoltage from a power source. In examples where each of the firstelectrode 260 and the second electrode 265 is provided a voltage, thedischarge chamber itself can be electrically coupled to ground. In someexamples, the chamber 250 may not be conductive, and the firstelectrodes 260 and second electrode 265 can be used to sustain a plasmadischarge 275. The voltages provided to the electrodes 260, 265 can bethe same or can be different and may be different for differentanalytes. Similarly, different voltages can be provided to theelectrodes 260, 265 when different plasma gases are introduced into thechamber 250 through an inlet 252.

In some examples, the discharge chamber or tube may comprise one or morebends which can enhance removal of metastable atoms or free electrons orboth. Referring to FIG. 3A, a discharge chamber 310 is shown comprisinga first region 312 and a second region 314. An inlet 311 is present inthe first region 312, and an outlet 315 is present in the second region314. A longitudinal axis of the second region 314 is generallyorthogonal to a longitudinal axis of the first region 312. The chamberof FIG. 3A comprises a “hard bend” in that the transition from the firstregion 312 to the second region 314 is abrupt. Depending on theparticular interfering species that are present in an analyte sample, itmay be desirable to include a hard bend in a discharge tube to enhanceremoval of the interfering species, as some interfering species maygenerally adopt a linear path from the inlet 311 and strike theorthogonal surface of the second region 314. In contrast, analyte ionscan be entrained in the flowing plasma gas and exit the chamber throughthe outlet 315. In some embodiments, an inner diameter of the firstregion 312 and second region 314 can be the same. In other embodiments,an average inner diameter of the first region 312 is smaller than anaverage inner diameter of the second region 314. In yet other instances,an average inner diameter of the first region 312 is greater than anaverage inner diameter of the second region 314. The inner diameter ofeach of the regions 312, 314 need not be constant along the length ofeach region but can vary if desired. The materials present in the firstregion 312 and the second region 314 may also be the same or may bedifferent. The overall shapes of the regions 312, 314 may also be thesame or may be different. Further, the exact length or other dimensionsof the hard bend area may vary. While not shown, one or more electrodesmay be used with the chamber 310, e.g., a voltage can be provided to theelectrode and used with the chamber 310 to sustain a plasma dischargewithin some portion of the chamber 310. The chamber 310 may beconductive or non-conductive depending on the other components that areused with the chamber 310. Where an electrode is used with the chamber310 it is typically positioned adjacent or near an inlet of the firstregion 312, though this positioning is not required.

In certain embodiments, a discharge chamber or tube may comprise a softbend rather than a hard bend. Referring to FIG. 3B, a discharge chamberor tube 350 is shown comprising a first region 352 and a second region354. An inlet 351 is present in the first region 352, and an outlet 355is present in the second region 354. A longitudinal axis of the secondregion 354 is also generally orthogonal to a longitudinal axis of thefirst region 352. The chamber of FIG. 3B comprises a “soft bend” in thatthe transition from the first region 352 to the second region 354 isgradual and is similarly shaped to a 90-degree elbow commonly used asfluid couplers in plumbing or tubing connections. Depending on theparticular interfering species that are present in an analyte sample, itmay be desirable to include a soft bend in a discharge chamber toenhance removal of the interfering species, as some interfering speciesmay be removed in the presence of a soft bend. Analyte ions can beentrained in the flowing plasma gas and exit the chamber through theoutlet 355. In some embodiments, an inner diameter of the first region352 and second region 354 can be the same. In other embodiments, anaverage inner diameter of the first region 352 is smaller than anaverage inner diameter of the second region 354. In yet other instances,an average inner diameter of the first region 352 is greater than anaverage inner diameter of the second region 354. The inner diameter ofeach of the regions 352, 354 need not be constant along the length ofeach region but can vary if desired. The materials present in the firstregion 352 and the second region 354 may also be the same or may bedifferent. The overall shapes of the regions 352, 354 may also be thesame or may be different. Further, the exact length or other dimensionsof the soft bend area may vary. While not shown, one or more electrodesmay be used with the chamber 350, e.g., a voltage can be provided to theelectrode and used with the chamber 350 to sustain a plasma dischargewithin some portion of the chamber 350. The chamber 350 may beconductive or non-conductive depending on the other components that areused with the chamber 350. Where an electrode is used with the chamber350 it is typically positioned adjacent or near an inlet of the firstregion 352, though this positioning is not required. The exact anglethrough which the soft bend curves may vary, for example, from about 60degrees to about 90 degrees.

In some embodiments, the discharge chamber or tube may comprise morethan a single bend. By including more than one bend, removal ofinterfering species such as, for example, metastable atoms, freeelectrons and photons can be improved so analyte molecules exiting thedischarge chamber or tube substantially free of these interferingspecies. Referring to FIG. 4A, a discharge chamber or tube 410 is shownthat comprises an inlet 411, a first region 412, a first bend 413, asecond region 414 coupled to the first region 412 through the first bend413, a second bend 415 and a third region 416 coupled to the secondregion 414 through the second bend 415. The third region 416 comprisesan outlet 417. While the bends 413, 415 shown in FIG. 4A are shown asboth being soft bends, it may be desirable to include one hard bend andone soft bend or two hard bends depending on the particular interferingspecies that might be present. Further, the overall length of the bends413, 415 need not be the same, and it may be desirable to lengthen thedownstream bend 415 to further enhance removal of interfering species.Similarly, it may be desirable to increase an overall inner diameter ofthe second bend 415 to alter the pressure flow at that end of thedischarge chamber 410. For example, by increasing a diameter of thesecond bend 415 and the third region 416, the gas flows and pressures inthe chamber 410 can be altered to promote laminar flow or some othertype of desired flow. While not shown, one or more electrodes may beused with the chamber 410, e.g., a voltage can be provided to theelectrode and used with the chamber 410 to sustain a plasma dischargewithin some portion of the chamber 410. The chamber 410 may beconductive or non-conductive depending on the other components that areused with the chamber 410. Where an electrode is used with the chamber410 it is typically positioned adjacent or near the inlet 411 of thefirst region 412, though this positioning is not required.

In certain examples, a discharge tube or chamber may comprise three ormore bends. Referring to FIG. 4B, a discharge chamber or tube 450 isshown that comprises an inlet 451, a first region 452, a first bend 453,a second region 454 coupled to the first region 452 through the firstbend 453, a second bend 455, a third region 456 coupled to the secondregion 454 through the second bend 455, a third bend 457, and a fourthregion 458 coupled to the third region 456 through the third bend 457.The fourth region 458 comprises an outlet 459. While the bends 455 and457 shown in FIG. 4B are shown as being soft bends, it may be desirableto include more than one hard bend depending on the particularinterfering species that might be present. Further, the overall lengthof the bends 453, 455, 457 need not be the same, and it may be desirableto lengthen the downstream bend 457 to further enhance removal ofinterfering species. Similarly, it may be desirable to increase anoverall inner diameter of the third bend 457 to alter the pressure flowat that end of the discharge chamber 450. For example, by increasing adiameter of the third bend 457 and the fourth region 458, the gas flowsand pressures in the chamber 450 can be altered to promote laminar flowor some other type of desired flow. While not shown, one or moreelectrodes may be used with the chamber 450, e.g., a voltage can beprovided to the electrode and used with the chamber 450 to sustain aplasma discharge within some portion of the chamber 450. The chamber 450may be conductive or non-conductive depending on the other componentsthat are used with the chamber 450. Where an electrode is used with thechamber 450 it is typically positioned adjacent or near the inlet 451 ofthe first region 452, though this positioning is not required.

In certain embodiments, the discharge chamber or tube may comprise twoor more bends whose orientations differ. By including more than one bendwith a different orientation, enhanced removal of interfering speciessuch as, for example, metastable atoms, free electrons and photons canbe achieved so analyte molecules exiting the discharge chamber or tubesubstantially free of these interfering species. Referring to FIG. 4C, adischarge chamber or tube 470 is shown that comprises an inlet 471, afirst region 472, a first bend 473, a second region 474 coupled to thefirst region 472 through the first bend 473, a second bend 475, a thirdregion 476 coupled to the second region 474 through the second bend 475,and a fourth region 478 coupled to the third region 476 through a bend477. The fourth region 478 comprises an outlet 479. While the bends 473,475, and 477 shown in FIG. 4C are all shown as being soft bends, it maybe desirable to include one hard bend and two soft bends or two hardbends depending on the particular interfering species that might bepresent. Further, the overall length of the bends 473, 475, 477 need notbe the same, and it may be desirable to lengthen the downstream bend 477to further enhance removal of interfering species. Similarly, it may bedesirable to increase an overall inner diameter of the bend 477 to alterthe pressure flow at that end of the discharge chamber 470. For example,by increasing a diameter of the third bend 477 and the third region 476and fourth region 478, the gas flows and pressures in the chamber 470can be altered to promote laminar flow or some other type of desiredflow. In this illustration the bend 473 may be considered a +90 degreebend, and the bend 475 may be considered a −90 degree bend. By alteringthe gas flow direction with the different orientations of the bends 473,475, enhanced collision of interfering species with the walls of chamber470 can be achieved, which can act to remove these interfering species.Analyte ions may be entrained within a central gas flow which moves downthe chamber 470 and exits through the outlet 479. While not shown, oneor more electrodes may be used with the chamber 470, e.g., a voltage canbe provided to the electrode and used with the chamber 470 to sustain aplasma discharge within some portion of the chamber 470. The chamber 470may be conductive or non-conductive depending on the other componentsthat are used with the chamber 470. Where an electrode is used with thechamber 470 it is typically positioned adjacent or near the inlet 471 ofthe first region 472, though this positioning is not required.

In some examples, the discharge chambers described herein may comprisemore than a single inlet. Referring to FIG. 5A, a discharge chamber 510comprises a first inlet 511 and a second inlet 513 and an outlet 515. Insome examples, the inlets 511, 513 can be fluidically coupled todifferent plasma gases so only one plasma gas may enter into the chamber510 at any time. In other instances, the inlets 511, 513 can be used tosimultaneously introduce two different plasma gases into the chamber510. The pressures and flow rates of the different plasma gases may bethe same or different, and inline mixing of the two gases may beaccomplished within the chamber 510.

In other configurations, a sample can be introduced through one of theinlets 511, 513 and a plasma gas can be introduced into the other of theinlets 511, 513. The configuration of FIG. 5A would introduce the sampleinto the chamber coaxially with the plasma gas through the inlets 511,513. If desired, however, one of the plasma gas and sample could beintroduced into the chamber in a non-coaxial manner. For example andreferring to FIG. 5B, a chamber 550 is shown that comprise a first inlet551 and a second inlet 553 and an outlet 555. The second inlet 553 isgenerally orthogonal to the first inlet 551. If desired, two differentplasma gases could be introduced through the inlets 551, 553 and anotherinlet could be present to introduce sample into the chamber 550. Theadditional inlet for the sample may be coaxial with the inlet 551 or theinlet 553 or could be positioned at a different angle with respect tothe inlets 551, 553.

In some examples, a discharge chamber may comprise more than one outlet.Referring to FIG. 5C, a discharge chamber 570 is shown that comprises aninlet 572, a first outlet 574 and a second outlet 576. The first outlet574 and second outlet 576 can be positioned in many different positionsand one or more of the outlets 574, 576 can be blocked if desired soions only exit through one of the outlets 574, 576.

In certain examples, the discharge chambers described herein maycomprise a variable inner diameter at different portions of thedischarge chamber. Referring to FIG. 6A, a discharge chamber 605comprises an inlet 606 and an outlet 607. An inner diameter of thedischarge chamber 605 increases from the inlet 606 to the outlet 607. Ifdesired, however, an average inner diameter may decrease from the inlet606 to the outlet 607. The change in size of the inner diameter from oneend of the chamber 605 to the other end of the chamber 605 need not belinear or conical and may instead be bell shaped or take other forms andshapes as desired.

In some examples, the inner diameter of the discharge chamber may bevariable at different portions of the discharge chamber. Referring toFIG. 6B, a discharge chamber 610 comprises an inlet 611 and an outlet612. The inner diameter of the chamber 610 increases from the inlet 611toward a central portion of the chamber 610 and then decreases towardthe outlet 612 of the chamber 610. The change in inner diameter need notbe linear or conical and may not be the same on each side of the chamber610. For example and referring to FIG. 6C, a distance d1 from a centrallongitudinal axis 625 of a chamber 620 may be substantially constantalong a longitudinal direction of the chamber 620, and a distance d2from the central longitudinal axis 625 to the other side of the chamber620 and vary along the longitudinal direction of the chamber 620.

In certain embodiments, a discharge chamber comprising one or more bendsmay also comprise a variable inner diameter along the length of thechamber. Referring to FIG. 6D, a discharge chamber 630 comprises a firstregion 631 (which may comprise an inlet), a bend 632 and a second region633 (which may comprise an outlet) coupled to the first region 631through the bend 632. An inner diameter of the second region 633 is (onaverage) greater than an inner diameter of the first region 631. Byincreasing the inner diameter from the first region 631 to the secondregion 633, it can be possible to alter the flow characteristics throughthe chamber 630 such that certain interfering species are removed and donot exit the chamber 630 to any substantial degree. In other instances,an inner diameter from an inlet end to an outlet end of the dischargechamber may decrease. The chamber 630 also comprises a third region 635coupled to the second region 633 through a bend 634. An inner diameterof the third region 635 may be larger than an inner diameter of thesecond region 633 to alter the flow characteristics through thedischarge chamber 630.

In certain configurations, two or more of the discharge chambers can befluidically coupled to each other to permit analyte ions to travel fromone chamber to another chamber. For example and referring to FIG. 7A, afirst discharge chamber 710 is shown as being coupled to a seconddischarge chamber 720 through an interface 715. Sample and/or plasma gasmay enter into the assembly through an inlet or inlets of the chamber710. If desired, the interface 715 could be omitted and a terminal endof the discharge chamber 710 could be sized and arranged to couple to aupstream end of the chamber 720 through a friction fit, e.g., byplugging the first chamber 710 into the second chamber 720. The frictionfit may be suitably tight to retain the two chambers to each other orfasteners, adhesives, joints or fittings can be used to retain the twochambers 710, 720 to each other at least during analysis. In someinstances, the discharge chamber may be constructed and arranged as amodule which can couple to another modular discharge chamber to permitthe user to select the overall length and nature of the coupledassembly. While the two chambers 710, 720 are shown as beingsubstantially the same in FIG. 7A, this feature is not required.Referring to FIG. 7B, a straight discharge chamber 730 is shown as beingcoupled to a bent discharge chamber 740. Sample and/or plasma gas mayenter into the assembly through an inlet or inlets of the chamber 730.If desired, the orientation could be reversed so that sample and/orplasma gas would enter into chamber 740. The orientation of the coupledassembly also need not be the same.

In some embodiments, two or more discharge chambers arranged in aparallel manner may be coupled to an inlet of a mass analyzer. Referringto FIG. 7C, a first discharge chamber 770 and a second discharge chamber772 are shown. Each of the chambers 770, 772 is fluidically coupled toan upstream sample introduction device 765. The sample introductiondevice 765 can be configured to direct analyte to one or both of thechambers 770, 772. For example, the sample introduction device maycomprise a solenoid valve which can fluidically couple and decouple thesample flow to one of the chambers 770, 772 or sample flow can be splitand provided to both chambers. The chambers 770, 772 could be configureddifferently so different analyte species can be provided to one of thedifferent chambers. For example, it may be desirable to provide a firstanalyte to a straight chamber if it is believed few interfering speciesmay result from ionization using a plasma discharge sustained with thestraight chamber. For a second analyte, it may be desirable to provide asecond analyte to a bent chamber if it is believed more interferingspecies will be generated and need to be removed prior to exit of anyions from the chamber. The chambers 770, 772 may be fluidically coupledseparately to a downstream component, e.g., a mass analyzer, or can befluidically coupled to a downstream component through a common interface(not shown). While not shown, three, four or more chambers could bearranged in parallel. Further, any one parallel chamber may comprise asingle discharge chamber or two or more discharge chambers coupled toeach other.

In some configurations where two or more discharge chambers arefluidically coupled to each other, each of the discharge chambers may beconfigured to sustain a respective plasma discharge or only one of thedischarge chambers may be configured to sustain a plasma discharge. Insome examples, the two discharge chambers may use the same plasma gasbut a different voltage can be provided to each of the chambers (or anelectrode or electrodes of each chamber). In other examples, the twodischarge chambers may use different plasma gases and a similar voltagecan be provided to the chamber (or an electrode or electrodes of thechamber). In some embodiments, the two discharge chambers may usedifferent plasma gases and a different voltage can be provided to eachchamber (or an electrode or electrodes of each chamber). The use of twoserially arranged discharge chambers permits operation of one plasma ortwo plasmas depending on the desired analyte sample. In some examples,the more upstream discharge chamber (relative to the position of aninlet) can be used to sustain a plasma discharge, and the downstreamdischarge chamber may be used to provide additional length to removemore interfering species. In other instances, the more downstreamdischarge chamber can be used to sustain a plasma discharge, and theupstream discharge chamber may be used to mix sample with a gas or otherspecies. For example, different gases can be introduced into theupstream chamber along with the sample to mix the gases and sample priorto the mixture reaching a plasma discharge sustained in the downstreamchamber.

In certain embodiments, the exact plasma gas selected for use in thedischarge sources described herein may vary. The plasma gas may be, forexample, helium, neon, argon, krypton, xenon, nitrogen, nitric oxide,ammonia, oxygen, ozone, air, compressed air, hydrogen, methane, carbonmonoxide, carbon dioxide, and nitrogen dioxide. Other gases are alsopossible. In some examples, two or more of these gases can be used in agas mixture to sustain a plasma discharge within a discharge chamber.The gas composition can be varied with different analytes species in asample if desired. For example, a first gas can be used to sustain aplasma discharge when a first analyte is introduced into the dischargechamber. Once the first analyte is ionized and exits the chamber, asecond gas can then be introduced to sustain a plasma discharge when thesecond analyte is introduced into the discharge chamber. By selectingthe particular plasma gas, more selective ionization of each analyte ina sample can be achieved.

In some examples, the flow rate of the plasma gas can be selected toprovide a desired pressure within the discharge chamber. For example,the plasma discharge can be sustained at a pressure of about 10⁻³ Torrto about 100 Torr. The pressure need not be constant during operation ofthe plasma discharge. For example, for certain analytes it may bedesirable to operate the plasma discharge at higher or lower pressures.In some embodiments and without wishing to be limited by theseillustrative flow rates, the gas flow rate into the discharge chambermay be, for example, about 500 standard cubic centimeters per minute(sccm), or less than 500 sccm or less than 150 sccm or less than 100sccm. In comparison to conventional inductively coupled plasmas, whichoften operate at argon flow rates of 15 Liters/minute or more, the gasflow rates used in the discharge chambers described herein aresignificantly lower, which can result in costs savings and moreefficient operation of the devices. It is a significant attribute thatthe plasma discharge can be sustained using such low flow rates. Ifdesired, the discharge chamber may also be heated or cooled using gasesor external heating or cooling devices. For example, a heating orcooling device can be thermally coupled to the discharge chamber tocontrol the temperature of the discharge chamber. The heating or coolingdevice need not be thermally coupled to the entire chamber but may bethermally coupled, for example, to areas adjacent to the plasmadischarge to reduce the likelihood of melting of the chamber at theseareas.

In some embodiments, the discharge chambers described herein maycomprise one or more conductive materials or one or more areascomprising a conductive material. As noted in many instances, the entirechamber need not be conductive and the chamber can be renderedconductive using an electrode, a coating or by including conductivematerials at certain areas. In some examples, a conductive coating canbe present at an inlet end and at a region downstream of the inlet end.The inlet end may be electrically coupled to a power source, and thedownstream region can be electrically coupled to a power source orground. If desired, the entire chamber could be constructed of aconductive material. Notwithstanding the conductive materials can beplaced and arranged in many different ways in the chamber, theconductive material may comprise one or more of a stainless steel, anickel chromium alloy, nickel chromium molybdenum alloy, titanium, atitanium alloy, a lanthanide, a lanthanide alloy, an actinide, anactinide alloy and combinations thereof. While these materials are notrequired, high temperature metal-based materials can have increasedlifetimes and reduced maintenance needs.

In some instances where the discharge chamber comprises a metal, themetal may render the chamber optically opaque. If desired, an opticalwindow can be present in the discharge chamber to permit viewing of anyplasma discharge. Referring to FIG. 8, an optical window 820 is shown asbeing present toward an inlet end 812 of a discharge chamber 810. Theoptical window may comprise quartz or other optically transparentmaterials to permit a user to determine if the plasma discharge issustained within the chamber 810. An optical sensor can be present in adevice to receive light emissions from the plasma discharge as a safetymechanism. For example, if the plasma discharge extinguishes, an opticalsensor may be present and can be configured to turn off the voltageprovided to the chamber (or an electrode used with the chamber) as asafety mechanism. In addition, the sensor may switch off any plasma gasflow to conserve the gas. During ignition of the plasma, there may be atime window where the optical sensor is disabled to permit gas flow andplasma ignition prior to the safety sensor initiating termination of thevoltage and/or plasma gas flow. In other instances, no optical windowmay be present, and the current provided to the chamber (or an electrodeused with the chamber) can be monitored to determine if the plasmadischarge is sustained or has been extinguished.

In some configurations, the exact voltage provided to the conductiveregion or electrodes used in the discharge chambers described herein mayalso vary. As noted herein, the voltage can change with differentanalytes and/or different plasma gases. The voltage provided may beprovided from a direct current source, an alternating current source ora radio frequency source. Where a direct current voltage is used, thevoltage may vary from about 10 Volts to about 5000 Volts. The directcurrent voltage can be positive or can be negative, e.g., +/10 Volts to+/−5000 Volts. Where an alternating current voltage can be used, thealternating current may vary, for example, from about 20 Volts to about3000 Volts. The alternating current voltage can be positive or can benegative, e.g., +/20 Volts to +/−3000 Volts. Where a radio frequencycurrent is used, the radio frequency range may be from about 100 Hz toabout 10 MHz. The voltages values listed herein are provided forillustration purposes only and not intended to limit the exact voltagevalues that may be used. If desired, different types of current can beused with different analytes. For example, as a first analyte isintroduced into the discharge chamber, a plasma discharge can besustained using an alternating current to ionize the first analyte. As asecond analyte is introduced into the discharge chamber, a directcurrent can be used to sustain a plasma discharge to ionize the secondanalyte. In examples where two or more discharge chambers are coupled toeach other, one of the discharge chambers can use a first type ofvoltage to sustain a first plasma discharge and the other dischargechamber can use a different type of voltage to sustain a second plasmadischarge.

In certain examples, the discharge chambers described herein can be usedin a system comprising one or more other components. For example, thedischarge chamber may be fluidically coupled to an upstream componentthat can provide an analyte to the inlet of the discharge chamber and/orcan be fluidically coupled to a downstream component to provide ions tothe downstream component for analysis or further use. Referring to FIG.9A, a discharge chamber 930 is shown as being fluidically coupled to agas chromatography system. The gas chromatography system comprises aninjector 905 fluidically coupled to a column 910 positioned in an oven915. The injector 905 and/or column 910 are also fluidically coupled toa mobile phase 925, i.e. a gas, which can be used with a stationaryphase of the column 910 to separate two or more analytes in anintroduced sample. As individual analytes elute from the column 910,they can be provided to an inlet of the discharge chamber 930 forionization. As shown in FIG. 9A, the inlet to introduce sample isdifferent than an inlet 932 for introducing a plasma gas, though thesample inlet could be the same if desired. While the column 910 is shownas being directly coupled to an inlet of the discharge chamber 930, oneor more transfer lines, interfaces, etc. could instead be used. Forexample, a transfer line 940 can be used to fluidically couple thecolumn 910 to an inlet of the discharge chamber 930. The transfer line940 may be heated (if desired or needed) to maintain the analytes in thegas phase. Additional components may also be present between the column910 and the chamber 930, e.g., interfaces, splitters, an opticaldetection cell, concentration chambers, filters and the like.

In some embodiments, a discharge chamber can be fluidically coupled to aliquid chromatography (LC) system. Referring to FIG. 9B, a LC systemcomprises an injector 955 fluidically coupled to a column 960 throughone or more pumps 957. The injector 955 and/or column 960 are alsofluidically coupled to a mobile phase, i.e. a liquid, and the one ormore pumps 957 which can be used to pressurize the LC system. The column960 typically comprises a stationary phase selected to separate two ormore analytes in an introduced sample. As individual analytes elute fromthe column 960, they can be provided to an inlet of a discharge chamber970 for ionization. While the column 960 is shown as being directlycoupled to an inlet of the discharge chamber 970, one or more transferlines, interfaces, etc. could instead be used. For example, a flowsplitter can be used if desired. Additional components may also bepresent between the column 960 and the chamber 970, e.g., interfaces,splitters, an optical detection cell, concentration chambers, filtersand the like. As shown in FIG. 9B, an inlet for introducing the samplefrom the LC system is different than an inlet 972 for introducing aplasma gas, though they may be the same if desired.

In some examples, the discharge chamber can be present in a massspectrometer. For example, the discharge chambers disclosed herein mayalso be used in or with a mass analyzer. In particular the massspectrometer may include one or more discharge chambers directly coupledto an inlet of a mass analyzer or spatially separated from an inlet of amass analyzer. An illustrative MS device is shown in FIG. 10. A MSdevice 1000 includes a sample introduction device 1010, a dischargechamber 1015, a mass analyzer 1020, a detection device 1030, a processor1040 and an optional display (not shown). The mass analyzer 1020 and thedetection device 1030 may be operated at reduced pressures using one ormore vacuum pumps and/or vacuum pumping stages as noted in more detailbelow. The sample introduction device 1010 may be a GC system, an LCsystem, a nebulizer, aerosolizer, spray nozzle or head or other deviceswhich can provide a gas or liquid sample to the discharge chamber 1015.Where solid samples are used the sample introduction device 1010 maycomprise a direct sample analysis (DSA) device or other devices whichcan introduce analyte species from solid samples. The discharge chamber1015 may be any of those described herein or other suitable dischargechambers. The mass analyzer 1020 can take numerous forms dependinggenerally on the sample nature, desired resolution, etc. and exemplarymass analyzers are discussed further below. The detection device 1030can be any suitable detection device that can be used with existing massspectrometers, e.g., electron multipliers, Faraday cups, coatedphotographic plates, scintillation detectors, etc. and other suitabledevices that will be selected by the person of ordinary skill in theart, given the benefit of this disclosure. The processor 1040 typicallyincludes a microprocessor and/or computer and suitable software foranalysis of samples introduced into the MS device 1000. If desired, oneor more databases can be accessed by the processor 1040 fordetermination of the chemical identity of species introduced into the MSdevice 1000. Other suitable additional devices known in the art can alsobe used with the MS device 1000 including, but not limited to,autosamplers, such as AS-90plus and AS-93plus autosamplers commerciallyavailable from PerkinElmer Health Sciences, Inc.

In certain embodiments, the mass analyzer 1020 of MS device 1000 cantake numerous forms depending on the desired resolution and the natureof the introduced sample. In certain examples, the mass analyzer is ascanning mass analyzer, a magnetic sector analyzer (e.g., for use insingle and double-focusing MS devices), a quadrupole mass analyzer, anion trap analyzer (e.g., cyclotrons, quadrupole ions traps),time-of-flight analyzers (e.g., matrix-assisted laser desorbedionization time of flight analyzers), and other suitable mass analyzersthat can separate species with different mass-to-charge ratios. As notedin more detail below, the mass analyzer may comprise two or moredifferent devices arranged in series, e.g., tandem MS/MS devices ortriple quadrupole devices, to select and/or identify the ions that arereceived from the discharge chamber 1015.

In certain other examples, the discharge chambers disclosed herein maybe used with existing ionization methods used in mass spectroscopy. Forexample, a MS instrument with a dual source where one of the sources isa discharge chamber as described herein and the other source is adifferent ionization source can be assembled. The different ionizationsource may be, for example, an electron impact source, a chemicalionization source, a field ionization source, desorption sources suchas, for example, those sources configured for fast atom bombardment,field desorption, laser desorption, plasma desorption, thermaldesorption, electrohydrodynamic ionization/desorption, etc., thermosprayor electrospray ionization sources or other types of ionization sources.By including two different ionization sources in a single instrument, auser can select which particular ionization methods may be used.

In accordance with certain other examples, the MS systems disclosed herecan be hyphenated with one or more other analytical techniques. Forexample, a MS system can be hyphenated one or more devices forperforming liquid chromatography, gas chromatography, capillaryelectrophoresis, and other suitable separation techniques. When couplingan MS device to a gas chromatograph, it may be desirable to include asuitable interface, e.g., traps, jet separators, etc., to introducesample into the MS device from the gas chromatograph. When coupling anMS device to a liquid chromatograph, it may also be desirable to includea suitable interface to account for the differences in volume used inliquid chromatography and mass spectroscopy. For example, splitinterfaces can be used so that only a small amount of sample exiting theliquid chromatograph is introduced into the MS device. Sample exitingfrom the liquid chromatograph may also be deposited in suitable wires,cups or chambers for transport to the discharge chamber of the MSdevice. In certain examples, the liquid chromatograph may include athermospray configured to vaporize and aerosolize sample as it passesthrough a heated capillary tube. Other suitable devices for introducingliquid samples from a liquid chromatograph into a MS device, or otherdetection device, will be readily selected by the person of ordinaryskill in the art, given the benefit of this disclosure.

In certain examples, an MS device that includes a discharge chamber maybe hyphenated to at least one other MS device, which may or may notinclude its own discharge chamber, for tandem mass spectroscopyanalyses. For example, one MS device can include a first type of massanalyzer and the second MS device can include a different or similarmass analyzer than the first MS device. In other examples, the first MSdevice may be operative to isolate the molecular ions, and the second MSdevice may be operative to fragment/detect the isolated molecular ions.It will be within the ability of the person of ordinary skill in theart, to design hyphenated MS/MS devices at least one of which includes adischarge chamber. In some examples, the MS device may comprise two ormore quadrupoles which can be configured the same or different. Forexample, a triple quadrupole assembly as shown in the examples appendedhereto may be used to select ions from an ion beam exiting a dischargechamber.

In certain examples, the methods and systems herein may comprise or usea processor, which can be part of the system or instrument or present inan associated device, e.g., computer, laptop, mobile device, etc. usedwith the instrument. For example, the processor can be used to controlthe provided voltages to the discharge chamber and any electrodes, cancontrol the mass analyzer and/or can be used by the detector. Suchprocesses may be performed automatically by the processor without theneed for user intervention or a user may enter parameters through userinterface. For example, the processor can use signal intensities andfragment peaks along with one or more calibration curves to determine anidentity and how much of each molecule is present in a sample. Incertain configurations, the processor may be present in one or morecomputer systems and/or common hardware circuitry including, forexample, a microprocessor and/or suitable software for operating thesystem, e.g., to control the sample introduction device, ionizationdevice, mass analyzer, detector, etc. In some examples, the detectiondevice itself may comprise its own respective processor, operatingsystem and other features to permit detection of various molecules. Theprocessor can be integral to the systems or may be present on one ormore accessory boards, printed circuit boards or computers electricallycoupled to the components of the system. The processor is typicallyelectrically coupled to one or more memory units to receive data fromthe other components of the system and permit adjustment of the varioussystem parameters as needed or desired. The processor may be part of ageneral-purpose computer such as those based on Unix, Intel PENTIUM-typeprocessor, Motorola PowerPC, Sun UltraSPARC, Hewlett-Packard PA-RISCprocessors, or any other type of processor. One or more of any typecomputer system may be used according to various embodiments of thetechnology. Further, the system may be connected to a single computer ormay be distributed among a plurality of computers attached by acommunications network. It should be appreciated that other functions,including network communication, can be performed and the technology isnot limited to having any particular function or set of functions.Various aspects may be implemented as specialized software executing ina general-purpose computer system. The computer system may include aprocessor connected to one or more memory devices, such as a disk drive,memory, or other device for storing data. Memory is typically used forstoring programs, calibration curves, and data values during operationof the discharge chamber and any instrument including the dischargechamber. Components of the computer system may be coupled by aninterconnection device, which may include one or more buses (e.g.,between components that are integrated within a same machine) and/or anetwork (e.g., between components that reside on separate discretemachines). The interconnection device provides for communications (e.g.,signals, data, instructions) to be exchanged between components of thesystem. The computer system typically can receive and/or issue commandswithin a processing time, e.g., a few milliseconds, a few microsecondsor less, to permit rapid control of the system. For example, computercontrol can be implemented to control sample introduction, plasma gasflows and pressures, detector parameters, etc. The processor typicallyis electrically coupled to a power source which can, for example, be adirect current source, an alternating current source, a battery, a fuelcell or other power sources or combinations of power sources. The powersource can be shared by the other components of the system. The systemmay also include one or more input devices, for example, a keyboard,mouse, trackball, microphone, touch screen, manual switch (e.g.,override switch) and one or more output devices, for example, a printingdevice, display screen, speaker. In addition, the system may contain oneor more communication interfaces that connect the computer system to acommunication network (in addition or as an alternative to theinterconnection device). The system may also include suitable circuitryto convert signals received from the various electrical devices presentin the systems. Such circuitry can be present on a printed circuit boardor may be present on a separate board or device that is electricallycoupled to the printed circuit board through a suitable interface, e.g.,a serial ATA interface, ISA interface, PCI interface or the like orthrough one or more wireless interfaces, e.g., Bluetooth, Wi-Fi, NearField Communication or other wireless protocols and/or interfaces.

In certain embodiments, the storage system used in the systems describedherein typically includes a computer readable and writeable nonvolatilerecording medium in which codes of software can be stored that can beused by a program to be executed by the processor or information storedon or in the medium to be processed by the program. The medium may, forexample, be a hard disk, solid state drive or flash memory. The programor instructions to be executed by the processor may be located locallyor remotely and can be retrieved by the processor by way of aninterconnection mechanism, a communication network or other means asdesired. Typically, in operation, the processor causes data to be readfrom the nonvolatile recording medium into another memory that allowsfor faster access to the information by the processor than does themedium. This memory is typically a volatile, random access memory suchas a dynamic random access memory (DRAM) or static memory (SRAM). It maybe located in the storage system or in the memory system. The processorgenerally manipulates the data within the integrated circuit memory andthen copies the data to the medium after processing is completed. Avariety of mechanisms are known for managing data movement between themedium and the integrated circuit memory element and the technology isnot limited thereto. The technology is also not limited to a particularmemory system or storage system. In certain embodiments, the system mayalso include specially-programmed, special-purpose hardware, forexample, an application-specific integrated circuit (ASIC) or a fieldprogrammable gate array (FPGA). Aspects of the technology may beimplemented in software, hardware or firmware, or any combinationthereof. Further, such methods, acts, systems, system elements andcomponents thereof may be implemented as part of the systems describedabove or as an independent component. Although specific systems aredescribed by way of example as one type of system upon which variousaspects of the technology may be practiced, it should be appreciatedthat aspects are not limited to being implemented on the describedsystem. Various aspects may be practiced on one or more systems having adifferent architecture or components. The system may comprise ageneral-purpose computer system that is programmable using a high-levelcomputer programming language. The systems may be also implemented usingspecially programmed, special purpose hardware. In the systems, theprocessor is typically a commercially available processor such as thewell-known Pentium class processors available from the IntelCorporation. Many other processors are also commercially available. Sucha processor usually executes an operating system which may be, forexample, the Windows 95, Windows 98, Windows NT, Windows 2000 (WindowsME), Windows XP, Windows Vista, Windows 7, Windows 8 or Windows 10operating systems available from the Microsoft Corporation, MAC OS X,e.g., Snow Leopard, Lion, Mountain Lion or other versions available fromApple, the Solaris operating system available from Sun Microsystems, orUNIX or Linux operating systems available from various sources. Manyother operating systems may be used, and in certain embodiments a simpleset of commands or instructions may function as the operating system.Further, the processor can be designed as a quantum processor designedto perform one or more functions using one or more qubits.

In certain examples, the processor and operating system may togetherdefine a platform for which application programs in high-levelprogramming languages may be written. It should be understood that thetechnology is not limited to a particular system platform, processor,operating system, or network. Also, it should be apparent to thoseskilled in the art, given the benefit of this disclosure, that thepresent technology is not limited to a specific programming language orcomputer system. Further, it should be appreciated that otherappropriate programming languages and other appropriate systems couldalso be used. In certain examples, the hardware or software can beconfigured to implement cognitive architecture, neural networks or othersuitable implementations. If desired, one or more portions of thecomputer system may be distributed across one or more computer systemscoupled to a communications network. These computer systems also may begeneral-purpose computer systems. For example, various aspects may bedistributed among one or more computer systems configured to provide aservice (e.g., servers) to one or more client computers, or to performan overall task as part of a distributed system. For example, variousaspects may be performed on a client-server or multi-tier system thatincludes components distributed among one or more server systems thatperform various functions according to various embodiments. Thesecomponents may be executable, intermediate (e.g., IL) or interpreted(e.g., Java) code which communicate over a communication network (e.g.,the Internet) using a communication protocol (e.g., TCP/IP). It shouldalso be appreciated that the technology is not limited to executing onany particular system or group of systems. Also, it should beappreciated that the technology is not limited to any particulardistributed architecture, network, or communication protocol.

In some instances, various embodiments may be programmed using anobject-oriented programming language, such as, for example, SQL,SmallTalk, Basic, Java, Javascript, PHP, C++, Ada, Python, iOS/Swift,Ruby on Rails or C# (C-Sharp). Other object-oriented programminglanguages may also be used. Alternatively, functional, scripting, and/orlogical programming languages may be used. Various configurations may beimplemented in a non-programmed environment (e.g., documents created inHTML, XML or other format that, when viewed in a window of a browserprogram, render aspects of a graphical-user interface (GUI) or performother functions). Certain configurations may be implemented asprogrammed or non-programmed elements, or any combination thereof. Insome instances, the systems may comprise a remote interface such asthose present on a mobile device, tablet, laptop computer or otherportable devices which can communicate through a wired or wirelessinterface and permit operation of the systems remotely as desired.

In certain examples, the processor may also comprise or have access to adatabase of information about molecules, their fragmentation patterns,and the like, which can include molecular weights, mass-to-charge ratiosand other common information. The instructions stored in the memory canexecute a software module or control routine for the system, which ineffect can provide a controllable model of the system. The processor canuse information accessed from the database together with one or softwaremodules executed in the processor to determine control parameters orvalues for different components of the systems, e.g., different plasmagas flow rates, different electrode voltages, different mass analyzerparameters, etc. Using input interfaces to receive control instructionsand output interfaces linked to different system components in thesystem, the processor can perform active control over the system. Forexample, the processor can control the detection device, sampleintroduction devices, discharge chambers, electrodes and othercomponents of the system.

In certain embodiments, the discharge chambers can be used in a methodthat includes ionizing an analyte by introducing the analyte into aplasma discharge sustained within a discharge chamber comprising a firstelectrode. The discharge chamber may be configured similarly to any ofthose described herein, e.g., one that comprises at least one inlet andat least one outlet. The plasma discharge can be sustained within thedischarge chamber by providing a voltage to the first electrode in thepresence of a plasma gas introduced into the discharge chamber throughthe at least one inlet of the discharge chamber. For example, a directcurrent voltage of about 10 Volts to about 5000 Volts provided to thefirst electrode can be used to sustain the plasma discharge within thedischarge chamber. An alternating current voltage of about 20 Volts toabout 3000 Volts provided to the first electrode can be used to sustainthe plasma discharge within the discharge chamber. A radio frequencycurrent can be provided to the first electrode in a radio frequencyrange of about 100 Hz to about 10 MHz to sustain the plasma dischargewithin the discharge chamber. The exact gas pressure used can vary andillustrative pressures include, but are not limited to, those which cansustain the plasma discharge within the discharge chamber at a suitablepressure to avoid extinguishing of the plasma discharge. In onenon-limiting illustration, a pressure of about 10⁻³-100 Torr can beused. In another non-limiting example, a plasma gas flow rate of 500sccm or less can be used to sustain the plasma discharge. As notedherein the discharge tube can be configured in many different mannersand may comprise a first section adjacent to the at least one inlet, athird section adjacent to the at least one outlet and a second sectionbetween the first section and the third section. If desired, an averageinner diameter of the third section is larger than an average innerdiameter of the second section.

In some examples, the parameters used to sustain the plasma dischargecan be selected to promote production of a parent analyte ion of theionized analyte to permit quantitation of the analyte using a parentanalyte ion mass-to-charge peak intensity. For example, the softerionization provided by the plasma discharge can be used to increase anamount of precursor ions which are produced as compared to an amount ofprecursor ions produced using, for example, electron ionization. Acurrent provided to the first electrode can be monitored to determine ifthe plasma discharge is sustained within the discharge chamber. As notedherein, two or more plasma gases, two or more chambers or two or moredifferent voltages can be used to sustain the plasma discharge. Theparameters may be altered between different analytes to provide forselective ionization of different analytes.

In some embodiments, a method comprises providing a discharge chamberconfigured to sustain a plasma discharge within the discharge chamber.The discharge chamber can be configured to electrically couple to atleast one electrode configured to couple to a power source. Thedischarge chamber may comprise at least one inlet, at least one outletand at least one optional bend between the at least one inlet and the atleast one outlet. The discharge chamber can be configured to sustain theplasma discharge within the discharge chamber using a voltage providedto the at least one electrode.

In some examples, a method of quantitating an analyte in a samplecomprises measuring a peak intensity of a parent analyte ion producedfrom ionization of the analyte after introducing the analyte into aplasma discharge produced within a discharge chamber by using anysuitable plasma gas flow rate such as, for example, a plasma gas flowrate of 500 sccm or less in one illustration, wherein the plasma gas isselected to enhance production of the parent analyte ion using theproduced plasma discharge.

In other examples, a method of ionizing of an analyte to enhanceproduction of a parent analyte ion comprises introducing the analyteinto a plasma discharge sustained in a discharge chamber using a plasmagas provided to the discharge chamber and a voltage provided to thedischarge chamber, wherein the plasma discharge is sustained within thedischarge chamber using any suitable plasma gas flow rate such as, forexample, a plasma gas flow of 500 sccm or less, and wherein the plasmadischarge comprises an average temperature of about 2000 Kelvin or less.

In some examples, a plasma discharge comprises an average temperature ofabout 2000 Kelvin or less, wherein the plasma discharge is sustainedwithin a discharge chamber using a voltage provided to the dischargechamber in the presence of a provided plasma gas at a plasma gas flowrate of 500 sccm or less.

In certain examples, the discharge chambers may be packed in a kit withinstructions for using for using the plasma discharge ionization sourceto provide a plasma discharge within the discharge chamber. For example,the instructions may permit an end user to retrofit an existinginstrument with the discharge chamber.

Certain specific examples are now described to illustrate further someof the novel aspects and features of the technology described herein.

Example 1

Referring to FIG. 11, an illustration is shown of a discharge chambercomprising a stainless steel chamber 1120. A gas chromatography (GC)inlet 1112 is fluidically coupled to a fluid transfer line 1114 totransfer analyte from the GC system to chamber 1120. A plasma gas entersthe chamber in the direction of arrow 1116. A probe comprising anelectrode 1118 is electrically coupled to a DC power source to provide avoltage to the electrode. Using the plasma gas and the electrode 1118 aplasma discharge 1122 can be sustained in the chamber 1120. The analytespecies from the GC can be ionized and may exit the chamber 1120 throughan outlet 1124 and be provided to a downstream mass analyzer.

Example 2

Referring to FIG. 12, an illustration is shown of a discharge chambercomprising a stainless steel chamber 1220. A gas chromatography (GC)inlet 1212 is fluidically coupled to a fluid transfer line 1214 totransfer analyte from the GC system to chamber 1220. A plasma gas entersthe chamber in the direction of arrow 1216 and passes through the fluidtransfer line 1214 into the chamber 1220. A probe comprising anelectrode 1218 is electrically coupled to a DC power source to provide avoltage to the electrode. Using the plasma gas and the electrode 1218 aplasma discharge 1222 can be sustained in the chamber 1220. The analytespecies from the GC can be ionized and may exit the chamber 1220 throughan outlet 1224 and be provided to a downstream mass analyzer.

Example 3

Different plasma gases can be selected based on their ionizationpotential. Table 1 shows some values for different plasma gases. Intable 1, E* represents energy of metastables, t_(ray) representsradiative lifetime and E^(i) represents ionization energy (of atomic ormolecular species).

TABLE 1 Gas E* (eV) t_(rad) (seconds) E^(i) (eV) He 19.82 7900 24.6 Ne16.61 430 21.6 Ar 11.55 45 15.76 Kr 9.92 85 14.0 Xe 8.32 150 12.13 N₂8.52 0.7 15.6 NO 4.7 0.2 9.26

Example 4

Referring to FIG. 13, an illustration is shown of a discharge chamber1310 directly coupled to an inlet of a mass analyzer 1320. An outlet ofthe discharge chamber 1310 is directly coupled to an inlet of a firstpumping stage 1322 to fluidically couple the outlet and the firstpumping stage 1322 (labeled as M0). The first pumping stage 1322 isfluidically coupled to a second pumping stage 1324 (labeled as M1), andthe second pumping stage 1324 is fluidically coupled to a third pumpingstage 1326 (labeled as M2). Each of the pumping stages can befluidically coupled to one or more pumps (as shown by the arrows in FIG.13) to reduce the pressure within the various pumping stages, thoughstage 1322 (labeled as M0) may not be fluidically coupled to any pumpsif desired. The third pumping stage 1326 is fluidically coupled to atriple quadrupole assembly 1330 that comprises a first quadrupole Q1, asecond quadrupole CC and a third quadrupole Q2. The second quadrupole CCcan be configured as a collision quadrupole, and the first quadrupole Q1and the third quadrupole Q2 can be configured to select ions from anincident ion beam. A detector (not shown) can be fluidically coupled toQ2 to receive the selected ions and determine how many ions are present.The mass analyzer 1330 need not include all stages or components shownin FIG. 13.

Example 5

FIG. 14 shows a mass spectrum for hexatriacontane (C₃₆H₇₄ MW=506.9)using electron ionization. No precursor ions are present in the massspectrum, which makes identification of this analyte only possible usingthe fragment ions. FIGS. 15A-15C show spectra for hexatriacontane (FIG.15A), tetracontane (FIG. 15B) and tetratetracontane (FIG. 15C) usingelectron ionization methods. All major fragments in the mass spectra arethose of hydrocarbons, which makes identification of the various speciesdifficult.

Example 6

Mass spectra were obtained for hexatriacontane (C₃₆H₇₄ MW=506.9) usingthe discharge tube and mass analyzer setup shown in FIG. 13. The voltageprovided to sustain the discharge was about −500 Volts. In the scan ofFIG. 16B, argon was used as the plasma gas at a flow rate of about 50sccm. Zero air was used in the scan of FIG. 16A and FIG. 16B. Argon wasused as a collision gas to obtain the scan shown in FIG. 16B. Theresults are shown in FIGS. 16A and 16B. FIG. 16C includes an electronionization scan for comparison.

Referring to FIG. 16A, a Q1MS full scan shows enhanced production ofprecursor ion (M⁺ and/or [M-H]⁺), whereas almost no precursor ion isobserved when conventional EI is used (FIG. 16C). A product ion scan(FIG. 16B) also shows that large amounts of the precursor ion arepresent. By enhancing precursor ion amounts, it is possible to use theprecursor ion to identify and/or quantify an amount of the molecule in asample.

When introducing elements of the examples disclosed herein, the articles“a,” “an,” “the” and “said” are intended to mean that there are one ormore of the elements. The terms “comprising,” “including” and “having”are intended to be open-ended and mean that there may be additionalelements other than the listed elements. It will be recognized by theperson of ordinary skill in the art, given the benefit of thisdisclosure, that various components of the examples can be interchangedor substituted with various components in other examples.

Although certain aspects, examples and embodiments have been describedabove, it will be recognized by the person of ordinary skill in the art,given the benefit of this disclosure, that additions, substitutions,modifications, and alterations of the disclosed illustrative aspects,examples and embodiments are possible.

1. A plasma discharge ionization source comprising a discharge chambercomprising a conductive area, wherein the discharge chamber isconfigured to sustain a plasma discharge within the discharge chamber,wherein the discharge chamber comprises at least one inlet configured toreceive a plasma gas and at least one outlet configured to provideionized analyte from the discharge chamber.
 2. The plasma dischargeionization source of claim 1, further comprising a first electrodeelectrically coupled to the discharge chamber, wherein the firstelectrode is configured to electrically couple to a power source.
 3. Theplasma discharge ionization source of claim 1, wherein the firstelectrode is positioned within the at least one inlet of the dischargechamber.
 4. The plasma discharge ionization source of claim 1, furthercomprising a second electrode electrically coupled to the dischargechamber.
 5. The plasma discharge ionization source of claim 1, furthercomprising at least one bend between the at least one inlet and the atleast one outlet, and wherein the at least one bend is configured toreduce a number of metastable atoms and free electrons and photonsexiting the discharge chamber through the at least one outlet.
 6. Theplasma discharge ionization source of claim 5, in which the at least onebend is configured as about a ninety-degree bend.
 7. The plasmadischarge ionization source of claim 5, further comprising a second bendpositioned upstream of the at least one bend or positioned downstream ofthe at least one bend.
 8. The plasma discharge ionization source ofclaim 3, wherein the discharge chamber comprises a conductive material.9. The plasma discharge ionization source of claim 3, wherein the inletis configured to simultaneously receive the plasma gas and a samplecomprising an analyte.
 10. The plasma discharge ionization source ofclaim 3, further comprising a second inlet separate from the inlet,wherein the second inlet is configured to provide a sample comprising ananalyte into the discharge chamber.
 11. The plasma discharge ionizationsource of claim 3, wherein the discharge chamber comprises a firstsection adjacent to the at least one inlet, a third section adjacent tothe at least one outlet and a second section between the first sectionand the third section.
 12. The plasma discharge ionization source ofclaim 11, wherein an average inner diameter of the third section islarger than an average inner diameter of the second section.
 13. Theplasma discharge ionization source of claim 12, wherein an average innerdiameter of the second section is larger than an average inner diameterof the first section.
 14. The plasma discharge ionization source ofclaim 1, wherein the discharge chamber further comprises a second inletconfigured to receive a second plasma gas.
 15. The plasma dischargeionization source of claim 1, wherein the discharge chamber isconfigured to sustain the plasma discharge without any inductivecoupling.
 16. The plasma discharge ionization source of claim 5, furthercomprising a second discharge chamber fluidically coupled to thedischarge chamber, wherein the second discharge chamber comprises atleast one bend between an inlet section and an outlet section of thesecond discharge chamber.
 17. The plasma discharge ionization source ofclaim 16, wherein the at least one bend of the second discharge chambercomprises a different geometry than the at least one bend of thedischarge chamber.
 18. The plasma discharge ionization source of claim17, further comprising an electrode electrically coupled to the seconddischarge chamber.
 19. The plasma discharge ionization source of claim18, wherein the second discharge chamber is configured to sustain aplasma discharge with a second plasma gas different than the plasma gas.20. The plasma discharge ionization source of claim 1, wherein thedischarge chamber is configured to receive two or more different plasmagases to selectively ionize different analyte species using thedifferent plasma gases. 21-50. (canceled)